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Jung et al. Soft Sci 2024;4:15 https://dx.doi.org/10.20517/ss.2024.02 Page 19 of 44

residues. These multifaceted challenges hinder the seamless development of robust and reliable wearable
salivary glucose sensing devices.

In the pursuit of creating a durable, dependable, and biocompatible electrochemical sensor wearable for
monitoring saliva glucose levels to aid in diabetes management, Bihar et al. have reported the development
of an enzymatic glucose sensor . Notably, this sensor is inkjet-printed on paper substrates, showcasing a
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novel approach in the ongoing efforts to advance diabetes-related biosensing technologies. The device
fabrication involved utilizing a commercially available PEDOT:polystyrene sulfonate (PSS) ink
(conductivity of 250 S/cm) that is suitable for inkjet printing. The configuration employed a three-electrode
system on glossy commercial paper [Figure 6A]. The biorecognition element, consisting of GO and a Fc
X
complex, was incorporated by printing an aqueous solution onto the WE. Fc, serving as an electron
mediator, enhances sensor selectivity and widens the operational range by molecularly connecting the
enzyme to the sensing electrode. However, due to the weak adhesion on surfaces and its potential toxicity
concerns, Fc is mixed with the polysaccharide and chitosan in a solution. A thin layer of Nafion was applied
to the three electrodes (WE, RE, and CE) as a robust barrier against potential interference from complex
biological environments or unspecified redox reactions during electrode operation. The device exhibits
operational capability within a range spanning from 0.025 to 0.9 mM, showcasing efficient sensitivity
towards glucose concentrations present in saliva. This sensitivity makes it suitable for detecting abnormal
glucose levels during screening processes. Even after one month of storage at room temperature under
vacuum, the sensors retain functionality, experiencing minimal performance loss (< 25%).

In pursuing diabetes management and prevention, a prevalent avenue involves developing wearable devices,
particularly in the form of mouthguards. These devices serve as user-friendly tools for real-time monitoring
of diabetes-related substances found in saliva. Ciui et al. introduce a cavitas-printed electrochemical sensor
for directly detecting salivary components . The sensor, characterized by high flexibility and bendability,
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is seamlessly integrated into a customized mouthguard positioned on a simulated jaw structure resembling
the human oral cavity. The disposable nature of the sensor allows easy attachment to and detachment from
the mouthguard, facilitating replacement as needed. The use of cost-effective printing techniques, rapid
measurement times, prolonged storage stability, and user-friendly operation adds to the attractiveness of
this innovative mouthguard sensor [Figure 6B]. Moreover, as depicted in Figure 6C, Arakawa et al. reported
a glucose sensor incorporated into a mouthguard design, enabling wireless monitoring of salivary glucose
concentration through a mobile terminal . The mouthguard sensor, evaluated using artificial saliva,
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demonstrates the capability to measure glucose concentrations within the range of 1.75-10,000 μmol/L,
covering salivary sugar concentrations from 20 to 200 μmol/L. Also, applying a cellulose acetate membrane
on the electrode functioned as an interference rejection membrane, effectively mitigating the influence of
contaminants such as ascorbic acid and uric acid, achieving a notable noise ratio suppression of 97.1%. In
in-vivo testing [Figure 6C], the current of the sensor stabilized in pure water before insertion into the oral
cavity of the subject. Upon placement, the output quickly rose to approximately 30 nA, gradually declining
and stabilizing steadily in about 20 min. Disruptions in output current due to the mouthguard device were
not observed. Utilizing the difference between the stable value in deionized water and the post-wearing
equilibrium, a glucose concentration in oral cavity saliva of 21.1 μmol/L was estimated, closely aligning with
the results from the glucose measurement kit and spectrophotometer at 17.6 μmol/L.

Explorations into health monitoring through saliva are broadening to encompass infants. There is ongoing
research in creating wireless pacifiers for the early monitoring of childhood health and for managing and
preventing diabetes-related conditions. Lim et al. presented a bioelectronic pacifier with smart, wireless
capabilities for monitoring salivary electrolytes in neonates . This device enables real-time, continuous
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